Hyperpolarized MRI for Brain Tumor

Overseen By Wendy Ma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Susan Chang

Disqualifiers: Congestive heart failure, Myocardial infarction, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: Varies based on standard treatment protocols

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the safety and effectiveness of a special type of MRI using hyperpolarized carbon C 13 pyruvate for diagnosing glioma, a type of brain tumor. The trial will test whether this imaging technique can better identify and understand gliomas before and after treatment. People with a confirmed glioma diagnosis, who have either had a past MRI showing the tumor or are about to start treatment, might be suitable candidates. This study could provide new insights into more accurate brain tumor diagnosis.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to benefit from this innovative imaging technique.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What prior data suggests that hyperpolarized carbon C 13 pyruvate MRI is safe for diagnosing glioma?

Research has shown that using hyperpolarized carbon C 13 pyruvate in MRI scans is generally safe for people. In earlier studies, this technique showed promise for noninvasive brain scans without major safety issues. Other studies suggest it is well-tolerated, with participants experiencing no significant side effects.

This method involves injecting a special substance to enhance MRI image clarity. This substance has been used in people without causing harmful effects. Although this trial is in an early phase focused on safety, previous data is reassuring and suggests that this imaging method is safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using hyperpolarized carbon C 13 pyruvate combined with MRI for brain tumors because it offers a novel way to visualize metabolic processes in real-time. Unlike traditional imaging techniques, which mainly focus on structural changes, this approach allows doctors to see how tumors are metabolically active, providing a clearer picture of how aggressive the cancer might be. This method could lead to faster and more accurate assessments of tumor behavior, potentially guiding more personalized treatment plans.

What evidence suggests that hyperpolarized MRI is effective for diagnosing glioma?

This trial will evaluate a special type of MRI using hyperpolarized carbon C 13 pyruvate, a promising method for diagnosing brain tumors like glioma. Participants will receive hyperpolarized carbon C 13 pyruvate intravenously and undergo MRI. This technique can highlight changes in brain cell energy use, aiding in clearer tumor identification. It is non-invasive, requiring no surgery or body entry. Early findings suggest it provides detailed insights into brain cell energy processing. This improved imaging could simplify tumor detection and understanding of their behavior without traditional invasive procedures. ^{3 6 7 8 9}

Who Is on the Research Team?

Susan Chang, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a life expectancy of more than 12 weeks and diagnosed with glioma, who are not HIV-positive, pregnant or breastfeeding. Participants must have adequate kidney function, no severe heart failure or recent heart attacks, and no other cancers except certain skin cancers or cervical carcinoma in-situ unless in remission for at least 3 years.

Inclusion Criteria

I am over 18 years old and expected to live more than 12 weeks.

Patients must sign an informed consent indicating that they are aware of the investigational nature of this study. Patients must sign an authorization for the release of their protected health information.

I don't have any severe illnesses that would interfere with the study's imaging tests.

Exclusion Criteria

Subjects must be excluded from participating in this study if they are not able to comply with study and/or follow-up procedures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Injection

Participants receive one or two hyperpolarized carbon C 13 pyruvate injections intravenously and undergo MRI

1 day

1 visit (in-person)

Treatment

Participants in Cohort II receive standard radiation and temozolomide treatment outside of this study

Varies based on standard treatment protocols

Post-Treatment Imaging

Participants in Cohort II undergo MRI 4 weeks after completion of cancer therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Hyperpolarized Carbon C 13 Pyruvate
• Magnetic Resonance Imaging

Trial Overview The trial tests the safety of using hyperpolarized carbon C 13 pyruvate MRI to diagnose gliomas. It involves patients already scheduled for standard treatment with radiation and temozolomide (Cohort 2), as well as those with evaluable disease based on prior MR scans (Cohort 1).

How Is the Trial Designed?

Group I: Cohort II (Hyperpolarized C13, MRI) Experimental Treatment 4 Interventions

Participants receive hyperpolarized carbon C 13 pyruvate IV and undergo MRI before treatment and 4 weeks after completion of cancer therapy given outside of this study.

Group II: Cohort I (Hyperpolarized C13, MRI) Experimental Treatment 2 Interventions

Participants receive hyperpolarized carbon C 13 pyruvate intravenously IV and undergo MRI. The second hyperpolarized 13 C injection/imaging will be started approximately 15 to 60 minutes after the first injection for those who are willing to receive two 13 C injections

Who Is Running the Clinical Trial?

Susan Chang

Lead Sponsor

Trials

5

Recruited

520+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The study demonstrated that hyperpolarized carbon-13 (HP-13C) metabolic imaging is safe and well-tolerated in pediatric patients with brain tumors, with no adverse events reported during the imaging process.

HP-13C imaging successfully showed the brain's metabolism of HP [1-13C]pyruvate, indicating its potential as a useful tool for assessing metabolic changes in pediatric CNS tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers. Autry, AW., Park, I., Kline, C., et al.[2022]

Hyperpolarized 13C-MRI, which enhances the detection of tumor metabolism by 4-5 orders of magnitude, can track the metabolism of hyperpolarized [1-13C]pyruvate in cancer patients, providing insights into tumor activity and response to treatment.

Combining HP 13C-MRI with traditional 1H-MRI allows for detailed anatomical imaging and functional tumor analysis, potentially enabling early identification of patients who are not responding to therapies, although cost and technical challenges need to be addressed for broader clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized Carbon-13 MRI in Breast Cancer. Woitek, R., Brindle, KM.[2023]

In a study involving seven treatment-naive patients with glioblastoma, hyperpolarized 13C MRI revealed that the bicarbonate-to-pyruvate ratio was significantly lower in tumors compared to normal brain tissue, indicating altered metabolism in glioblastoma.

The study found strong correlations between tumor lactate and bicarbonate signal intensities with pyruvate signal intensity, suggesting that hyperpolarized 13C MRI can effectively monitor metabolic changes in glioblastoma, which may aid in understanding tumor behavior and treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging Glioblastoma Metabolism by Using Hyperpolarized [1-13C]Pyruvate Demonstrates Heterogeneity in Lactate Labeling: A Proof of Principle Study. Zaccagna, F., McLean, MA., Grist, JT., et al.[2022]

A stable hyperpolarized solution of [1-(13)C]-ethyl pyruvate was successfully developed, allowing for its use in metabolic imaging studies.

In a study involving anesthetized rats, hyperpolarized [1-(13)C]-ethyl pyruvate was compared to [1-(13)C]-pyruvate, demonstrating its potential for effective uptake and metabolic imaging in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic imaging in the anesthetized rat brain using hyperpolarized [1-13C] pyruvate and [1-13C] ethyl pyruvate. Hurd, RE., Yen, YF., Mayer, D., et al.[2021]

The study introduces a new method called Signal Amplification By Reversible Exchange (SABRE) that allows for the rapid production of hyperpolarized pyruvate for MRI, achieving results in just 6 minutes, making it a faster and more accessible option for metabolic imaging.

The produced hyperpolarized pyruvate solution is sterile, non-toxic, and pH neutral, indicating its safety for use in living organisms, which enhances its potential for diagnosing and monitoring cancer and other diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Metabolic Imaging of [1-13 C]Pyruvate-d3 Hyperpolarized By Reversible Exchange With Parahydrogen. de Maissin, H., Groß, PR., Mohiuddin, O., et al.[2023]

Hyperpolarized carbon 13 MRI (13C MRI) is a groundbreaking imaging technique that allows for real-time, noninvasive observation of tissue metabolism, particularly useful in cancer research.

This method has shown promise in clinical applications such as tumor grading, tailoring treatment based on metabolic profiles, and detecting early treatment responses by monitoring metabolic changes before structural alterations in tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized Carbon 13 MRI: Clinical Applications and Future Directions in Oncology. Deen, SS., Rooney, C., Shinozaki, A., et al.[2023]

Hyperpolarized MRI using [1-13C] pyruvate can effectively characterize energy metabolism in the human brain and identify altered cancer metabolism in brain tumors, as evidenced by the production of HP lactate from HP pyruvate.

This method shows promise as a quantitative metabolic biomarker for assessing tumor response, correlating well with standard clinical imaging techniques like MRI and PET/CT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients. Miloushev, VZ., Granlund, KL., Boltyanskiy, R., et al.[2019]

Hyperpolarized [1-(13)C]pyruvate can effectively detect treatment responses in glioma tumors, which is challenging with traditional imaging methods like PET due to interference from normal brain tissue signals.

In a rat model, significant lactate labeling was observed in glioma tumors after treatment, with a notable decrease in the ratio of tumor lactate to blood pyruvate signal following whole brain irradiation, indicating a potential response to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detecting response of rat C6 glioma tumors to radiotherapy using hyperpolarized [1- 13C]pyruvate and 13C magnetic resonance spectroscopic imaging. Day, SE., Kettunen, MI., Cherukuri, MK., et al.[2021]

In a study involving three patients with glioblastoma, 13C MR spectroscopic imaging using hyperpolarized pyruvate successfully detected increased lactate production in tumor regions prior to surgical resection, indicating altered metabolism in these aggressive tumors.

The imaging technique correlated well with histological findings, confirming the presence of WHO grade IV glioblastoma and suggesting that this method could help identify metabolic changes associated with tumor aggressiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative imaging of glioblastoma patients using hyperpolarized 13C pyruvate: Potential role in clinical decision making. Chen, J., Patel, TR., Pinho, MC., et al.[2022]

This study is the first to use hyperpolarized 13C MRI to visualize and measure how the human brain processes [2-13C]pyruvate, providing insights into cerebral energy metabolism.

In a trial involving 5 healthy volunteers, the technique allowed for the simultaneous assessment of glycolytic and oxidative metabolism by quantifying the conversion rates of pyruvate to lactate and glutamate, highlighting its potential for advanced metabolic imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized [2-13C]pyruvate MR molecular imaging with whole brain coverage. Chung, BT., Kim, Y., Gordon, JW., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6050093/

Metabolic Imaging of the Human Brain with Hyperpolarized ... Here we present the first dynamically acquired human brain HP 13C metabolic spectra and spatial metabolite maps in cases of both untreated and recurrent tumors.

2. aacrjournals.org aacrjournals.org/cancerres/article/78/14/3755/631786/Metabolic-Imaging-of-the-Human-Brain-with

Metabolic Imaging of the Human Brain with Hyperpolarized 13 ... Hyperpolarized (HP) MRI using [1-13C] pyruvate is a novel method that can characterize energy metabolism in the human brain and brain tumors.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10546364/

Hyperpolarized Carbon 13 MRI: Clinical Applications and ... Hyperpolarized carbon 13 MRI (13C MRI) is a novel imaging approach that can noninvasively probe tissue metabolism in both normal and pathologic tissues.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2213158220301601

Characterization of serial hyperpolarized 13C metabolic ... Hyperpolarized carbon-13 (HP-13C) MRI is a non-invasive imaging technique for probing brain metabolism, which may improve clinical cancer surveillance.

5. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/rycan.240004

Hyperpolarized 13 C Pyruvate MRI: An Important Window ... HP 13C pyruvate MRI has successfully been used in numerous preclinical cancer models and recently, under investigational new drug (IND) approval ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11058429/

Hyperpolarized Carbon-13 Magnetic Resonance Imaging Hyperpolarized (HP) carbon-13 ( 13 C) MRI represents an innovative approach for noninvasive, real-time assessment of dynamic metabolic flux.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03565367

NCT03565367 | Hyperpolarized Carbon C 13 Pyruvate ... Hyperpolarized carbon C 13 pyruvate magnetic resonance imaging may be used to measure the metabolic state of malignant brain tumors. Detailed Description.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38205934/

13 C]pyruvate in D 2 O for hyperpolarized MRI of the brain: A ... HP [1- 13 C]pyruvate in D 2 O is safe for human imaging and provides an increase in T 1 and SNR that may improve image quality.

9. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/rycan.230005

Hyperpolarized Carbon 13 MRI: Clinical Applications and ... Hyperpolarized carbon 13 MRI ( 13 C MRI) is a novel imaging approach that can noninvasively probe tissue metabolism in both normal and pathologic tissues.